Vol.20 No.5

Original Article

Mizoribine protects against bleomycin-induced lung injury

Authors

Kiyoshi Matsui1 , Haruyasu Ueda2 , Makoto Terada3 , Naoto Azuma1 , Haruki Okamura4 , Hajime Sano1

  • Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine
  • Department of Pharmacy, Hyogo University of Health Sciences
  • Department of Allergology, Hyogo Prefectural Tsukaguchi Hospital
  • Institute for Advanced Medical Sciences, Hyogo College of Medicine
Received:

2 October 2009

Accepted:

16 April 2010

Published online:

21 May 2010

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Abstract

Bleomycin (BLM)-induced lung injury has become a model for studies of interstitial pneumonitis and pulmonary fibrosis. BLM induces lung injury in two phases: early inflammation characterized by infiltration of inflammatory cells into the lungs, followed by a late phase of fibrosis characterized by deposition of collagen. In this study, we examined the role of mizoribine (MZB) in the regulation of inflammatory tissue injury caused by BLM. We examined the role of MZB using a mouse model of BLM-induced lung injury. We demonstrated that mice subjected to instillation of BLM into the lungs had a significantly increased number of macrophages and lymphocytes in bronchoalveolar lavage fluid (BALF), but that those treated with MZB in the early phase showed a significant reduction in the total number of BALF macrophages and lymphocytes. However, MZB was unable to inhibit fibrosis in the late phase of BLM injury. Our findings suggest that MZB inhibits the proliferation of both lymphocytes and macrophages in the early phase of the BLM-induced acute inflammatory response, as well as its development and amplification, but does not inhibit fibrotic change in the late phase.

Key words

Interstitial pneumonia - Mizoribine - Bleomycin-induced lung injury - Inflammatory phase